Infection is a major cause of morbidity and mortality among patients with systemic lupus erythematosus (SLE). One objective of the proposed research is to examine in detail the nature, source and mechanism of action of a cationic protein that we have found in serum from some patients with SLE and that inhibits (in a uniquely specific and reversible fashion) the chemotactic activity of complement (C5)-derived peptides. Studies of patients with SLE have yielded evidence that this inhibitor may contribute (in part) to an increased susceptibility to severe bacterial infections. The other objective is to elucidate the mechanism of action of an anionic polypeptide ("cochemotaxin") that we have found in normal human serum (and plasma) and that permits low concentrations of C5a des Arg to exhibit chemotactic activity for polymorphonuclear leukocytes. We have found that the "complex" of C5a des Arg and its "cochemotaxin" probably accounts for most of the chemotactic activity that is generated in human serum after complement activation. Experiments will be performed to test the hypotheses that the "cochemotaxin" binds to the oligosaccharide portion of C5a des Arg and that the "cochemotaxin" (not C5a des Arg) is the "target" of the inhibitor in SLE serum. The studies outlined in this proposal should provide important new information that is relevant to host defense mechanisms in patients with SLE. It may be possible to explain (in part) why patients with SLE have an increased susceptibility to infections caused by pyogenic microorganisms. It also may be possible to identify patients with SLE who are at risk of developing life-threatening infections. On a more basic level, these studies should provide new information concerning structure-activity relationships of various biologically-active, complement-derived peptides. These studies also should yield new information that is fundamental to our understanding of mechanisms involved in regulating the biologic activities of complement-derived peptides.